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高度抗体溶液的粘度预测使用原子模拟
Tobias M Prass1, Patrick Garidel2, Michaela Blech2
1Center for Theoretical Chemistry, Ruhr University Bochum, D-44780 Bochum, Germany.
Journal of chemical information and modeling
|September 27, 2023
概括
计算方法现在可以预测密集蛋白质溶液的粘度,有助于生物制药的开发. 原子分子动力学模拟准确估计粘度,提供分子洞察力,但需要大量的计算资源.
科学领域:
- 生物物理学的生物物理.
- 计算化学的计算化学
- 材料科学 材料科学 材料科学
背景情况:
- 对密集蛋白质溶液的精确粘度预测对于生物制药配方开发至关重要.
- 实验性粘度测量通常受到高度样品可用性的限制.
研究的目的:
- 通过使用分子动力学 (MD) 模拟来计算预测密集单克隆抗体 (mAb) 溶液的动态粘度.
- 将模拟结果与实验测量结果进行比较,了解差异.
主要方法:
- 大规模的原子分子动力学 (MD) 模拟与明确的溶解.
- 格林-库博方法利用压力波动来计算粘度.
- 实验性粘度测量使用旋转类风湿学.
主要成果:
- MD模拟成功预测了高度 (200-250 mg/mL) 的mAb溶液的粘度.
- 计算粘度 (24mPa·s在250 mg/mL) 与实验值 (23mPa·s在213 mg/mL) 非常接近.
- 这些差异归因于模拟中对mAb-mAb相互作用的低估.
结论:
- 全原子MD模拟对于预测密度 mAb 溶液属性是可行的.
- 这项研究提供了对调节粘度的分子相互作用的微观见解.
- 对于高粘度系统的计算采样仍然存在挑战.
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